Inactivation of astrocytic glutamine synthetase by hydrogen peroxide requires iron

▶ H2O2 partly reduced the activity of purified GS and astrocytic GS. ▶ The inactivation of astrocytic GS was prevented by iron chelators. ▶ Cellular and purified GS were more extensively inactivated by H2O2 plus iron and ascorbate. ▶ Astrocytic GS is inactivated via the Fenton reaction. ▶ The lower specific GS activity observed in neurodegenerative conditions may be due to redox-active iron.